Cyclohexanone Oxime Synthesis Notes

Transcription

1 Reminder: These notes are meant to supplement, not replace, the laboratory manual. Cyclohexanone Oxime Synthesis Notes Application: Oximes are common chemical intermediates. The oxime we are making today is used commercially in the synthesis of Nylon-6 i. Nylon-6 is a major industrial chemical which is used to make car tire tread and shoe laces. Oximes have also shown to have promise as drugs which reduce the harmful impact from deliberate or accidental organophosphate poisoning ii. Organophosphates are used as chemical warfare agents and pesticides. Background: The carbonyl functional group has a large dipole. The carbon of the carbonyl carries a partial positive charge, the oxygen carries a partial negative charge. The carbon of a carbonyl is susceptible to nucleophilic attack which results in breaking the bond to oxygen and forming a tetrahedral intermediate. This is usually followed by a series of proton exchanges where the oxygen is converted to a better leaving group, then a new bond is formed from the nucleophile to the carbon reforming an sp 2 center and the oxygen simultaneously leaves. A wide variety of carbonyl derivatives are made by this same general reaction mechanism. In this experiment a cyclohexanone oxime will be formed from cyclohexanone and hydroxylamine. Cyclohexanone oxime will be synthesized, isolated, and analyzed by melting point determination. The percent yield and the purity of the product will be assessed. Overall Reaction: Page 1 of 5

2 Mechanism: 1. The overall reaction consists of two separate reactions. The first reaction is a simple acid-base reaction. The second reaction is a type of substitution reaction. 2. The first reaction in this experiment is an acid-base reaction between hydroxylamine hydrochloride salt and sodium hydroxide. Hydroxyl amine is packaged and sold as a solid salt, hydroxyl amine hydrochloride. This is commonly written as means that the HCl separates and the H associates with the nitrogen of the hydroxyl, it amine molecule forming a quaternary nitrogen salt. The Cl - is the counter ion. The quaternary nitrogen in has a formal plus one charge and has no available non-bonded electrons. This nitrogen is not nucleophilic. In the first acid-base reaction, the hydroxide from sodium hydroxide removes a proton (deprotonates) the quaternary amine salt and liberates or frees the hydroxyl amine reactant. The nitrogen on the resulting free hydroxyl amine (NH 2 -OH) now has one pair of non-bonded electrons on the nitrogen. This nitrogen is a very good nucleophile. 3. The nitrogen of the hydroxyl amine, NH 2 -OH is a stronger nucleophile than the adjacent oxygen because nitrogen is less electronegative and more willing to share electrons to form a covalent bond. Hence nitrogen and not oxygen is the active nucleophile. The nitrogen of hydroxyl amine attacks the carbon of the carbonyl. The carbon of the carbonyl within cyclohexanone is the electrophile. 4. The full mechanism is depicted below. Page 2 of 5

3 5. Neat Cyclohexanone is a clear liquid at room temperature with a density of g/ml iii. Pure cyclohexanone oxime is an opaque white solid at room temperature with a literature melting point of 90 o C iv. 6. The solubility of cyclohexanone oxime in water is much lower than the solubility of the parent cyclohexanone (<0.1 vs 8.7 grams per 100 ml). This fact allows the product to precipitate from the reaction solution and be isolated by vacuum filtration. Reaction and Useful Data Cyclohexanone hydroxylamine hydrochloride (Aq) Sodium Hydroxide (Aq) Cyclohexanone oxime M M 2.5 M dens g/ml m.wt g/mol g/mol 40.0g/mol g/mol b.p. 155 o C o C m.p o C 91 o C Solubility (g/100 ml) 8.7 v na na < 0.1 vi 7. Analogous reactions: There are many other similar reactions which proceed by the same general reaction mechanism vii. In each of these, the nucleophile attacks the carbon of the carbonyl. In many but not all of these the tetrahedral intermediate reacts further and a sp 2 hybridized carbon is reformed. Page 3 of 5

4 If the nucleophile is ammonia or a primary amine, an imine is produced. If the nucleophile is a secondary amine, an imine is first formed which tautomerizes into an enamine. If the nucleophile is a hydrazine, a hydrazone is formed. If the nucleophile is 2,4-Dinitrophenylhydrazine, 2,4-dinitrophenylhydrazone is formed. If the nucleophile is a semicarbazide, a semicarbazone is formed The mechanisms for the above transformations are all very similar to the mechanism for the oxime formation. Be sure you are familiar with these mechanisms and transformations References: i Weissermel, K., Arpe. H. R. Industrial Organic Chemistry, 3 rd, Wiley, 1997, pp ii Shrot, S. Markel, G., Dushnitsky, T., Krivoy,The possible use of oximes as antidotal therapy in organophosphate-induced brain damage, Neurotoxicology, A. 2009, 30(2), or iii Handbook of Chemistry and Physics, 65 th, CRC Press, Bocca Raton FL 1984,p C-451 iv Ibid C-252 Page 4 of 5

5 v ICSC Cyclohexanone, (September 27, 2017) Chemical book, vi (Accessed September 27, 2017) vii Klein, D., Organic Chemistry, Wiley, 2012, pp Revised October 4, 2017, S.L. Weaver Page 5 of 5